Monoclonal antibodies (MA) directed against tumor-associated antigens in bronchogenic carcinomas would be useful for early diagnosis of non-small cell tumors, that may then be surgically cured, or for the treatment of micrometastatic disease. Although a number of such antibodies have been reported, few have promise as therapeutic reagents due to lack of surface membrane expression or undesirable isotype (IgM) that may not adequately diffuse into extravascular spaces. We have produced and characterized one MA (503D8) that reacts with a surface membrane antigen of 15,000 daltons that is also secreted into cell culture supernatants. Immunoperoxidase staining of human tissues revealed markedly enhanced expression of the antigen in lung tumors compared with normal lung but sufficient expression in liver and kidney to render it unattractive as a therapeutic reagent. Another MA (353 H10), however, reacts predominantly with squamous cell carcinomas of the lung and displays only very minor reactivity with normal tissue (occasional distal tubules of kidney).